A Prospective, Multicenter, Randomized, Open-label, Active-controlled, Two-parallel Groups, Phase 3 Study to Compare the Efficacy and Safety of Masitinib to Sunitinib in Patients With Gastrointestinal Stromal Tumor After Progression With Imatinib at 400mg as First Line Treatment

GISTs are uncommon visceral sarcomas that arise predominantly in the gastrointestinal tract. Most GIST cells are positive for c-kit (CD117), a cell surface antigen corresponding to the Stem Cell Factor (SCF) receptor. The receptor has an intracellular tyrosine kinase (TK) joined by a juxtamembrane domain. It is hypothesized that all malignant GIST cells harbor a mutation of c-kit, resulting in the activation of c-kit and cell division and tumour growth.

Drugs that can selectively inhibit TKs are likely to be of benefit in GISTs. Masitinib (AB1010) is a TK inhibitor, selectively and effectively inhibiting c-kit. Imatinib is also a TK inhibitor indicated in the treatment of GIST. It might be associated with side effects and patients might develop a resistance to treatment over time. Based on pre-clinical and clinical studies, masitinib (AB1010) can be considered as a good candidate in the second line treatment of patients with GIST after progression with imatinib.

Patient after progression with to imatinib at the dose of 400 mg as first line treatment. Resistance Progression is defined as a RECIST 1.1 and/or CHOI disease progression while receiving imatinib treatment

Patient with ECOG ≤ 2

Patient with adequate organ functions

Patient with life expectancy > 6 months

Male or female patient, age >18 years

Patient with a BMI > 18 kg/m² and weighing at least 40 kg

Male and female patient of child bearing potential, (for female entering the study after a menstrual period and who have a negative pregnancy test at baseline) must agree to use two methods (one for the patient and one for the partner) of medically acceptable forms of contraception during the study and for 3 months after the last treatment intake.

Patient able and willing to comply with study procedures as per protocol

Patient able to understand, sign, and date the written informed consent form at screening visit prior to any protocol-specific procedures

Exclusion Criteria:

Patient treated for a cancer other than GIST within 5 years before enrolment, with the exception of basal cell carcinoma or cervical cancer in situ

Patient with active central nervous system (CNS) metastasis or with history of CNS metastasis

- Patient presenting with cardiac disorders defined by at least one of the following conditions:

Patient with cardiac failure class III or IV of the NYHA classification

Patient with severe conduction disorders which are not prevented by permanent pacing (atrio-ventricular block 2 and 3, sino-atrial block)

Syncope without known aetiology within 3 months

Uncontrolled severe hypertension, according to the judgment of the investigator, or symptomatic hypertension

Patient with history of poor compliance or history of drug/alcohol abuse, or excessive alcohol beverage consumption that would interfere with the ability to comply with the study protocol, or current or past psychiatric disease that might interfere with the ability to comply with the study protocol or give informed consent

Pregnant, or nursing female patient

Previous treatment

Known hypersensitivity to sunitinib or masitinib or to any of the excipients

Patient previously treated with a dose of imatinib > 400mg

Patient intolerant to imatinib

Previous treatment with sunitinib or kinase inhibitor other than imatinib

Wash-out

Treatment with any investigational agent within 4 weeks prior to baseline

Previous imatinib treatment should be permanently discontinued within 4 days prior randomisation and patient should have recovered from potential toxicity related to imatinib

Contacts and Locations

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Please refer to this study by its ClinicalTrials.gov identifier: NCT01694277